Physiology of dyspnea
- Richard M Schwartzstein, MD
Richard M Schwartzstein, MD
- Professor of Medicine
- Harvard Medical School
Breathing discomfort is one of the most common and distressing symptoms experienced by patients. While there are no symptom-specific data about the prevalence of this problem, the epidemiology of cardiac and pulmonary diseases indicates that the magnitude of the problem is large. Cardiac disease is the leading cause of death in the United States, and individuals with angina or myocardial infarction often experience breathlessness as the major (and sometimes sole) indicator that they are ill . In addition, asthma and chronic obstructive pulmonary disease (COPD) afflict approximately 34 million people in the United States, most of whom seek help from clinicians for relief of breathlessness [2,3].
Investigations of the language of dyspnea suggest that this symptom represents a number of qualitatively distinct sensations, and that the words utilized by patients to describe their breathing discomfort may provide insights into the underlying pathophysiology of the disease [4-7]. Furthermore, there is a growing recognition that one must distinguish between a "sensation" (the neural activation resulting from the stimulation of a receptor) and a "perception" (the reaction of the individual to that sensation) [8-10] and that healthcare providers are relatively poor at estimating the intensity of dyspnea by observing patients [11,12]. In addition, for a given intensity of a breathing sensation, the unpleasantness of the sensation may vary with the stimulus .
A consensus statement of the American Thoracic Society (ATS) has defined dyspnea as "a term used to characterize a subjective experience of breathing discomfort that is comprised of qualitatively distinct sensations that vary in intensity. The experience derives from interactions among multiple physiological, psychological, social, and environmental factors, and may induce secondary physiological and behavioral responses" .
The respiratory system is designed to maintain homeostasis with respect to gas exchange (adequate oxygenation) and the acid-base status of the organism (adjust arterial tension of carbon dioxide [PaCO2] to maintain normal pH). Derangements in oxygenation as well as acidemia lead to breathing discomfort. However, the development of dyspnea is a complex phenomenon which, in many patients, is the result of stimulation of a variety of mechanoreceptors throughout the upper airway, lungs, and chest wall, and which must also account for the sensations that arise when there is a mechanical load on the system (eg, increased airway resistance or decreased lung and/or chest wall compliance). The origins of dyspnea associated with the inadequate delivery of oxygen to, or utilization by, peripheral muscles are less well understood, but deserve consideration as well.
The ATS statement on the mechanisms, assessment, and management of dyspnea, as well as other ATS guidelines, can be accessed through the ATS web site at www.thoracic.org/statements.
- Cook DG, Shaper AG. Breathlessness, lung function and the risk of heart attack. Eur Heart J 1988; 9:1215.
- Centers for Disease Control and Prevention. Chronic obstructive pulmonary disease (COPD). http://www.cdc.gov/copd/data.htm (Accessed on April 21, 2016).
- Centers for Disease Control and Prevention. Asthma. http://www.cdc.gov/nchs/fastats/asthma.htm (Accessed on April 21, 2016).
- Simon PM, Schwartzstein RM, Weiss JW, et al. Distinguishable types of dyspnea in patients with shortness of breath. Am Rev Respir Dis 1990; 142:1009.
- Elliott MW, Adams L, Cockcroft A, et al. The language of breathlessness. Use of verbal descriptors by patients with cardiopulmonary disease. Am Rev Respir Dis 1991; 144:826.
- Mahler DA, Harver A, Lentine T, et al. Descriptors of breathlessness in cardiorespiratory diseases. Am J Respir Crit Care Med 1996; 154:1357.
- Schwartzstein RM. The language of dyspnea. In: Dyspnea: Mechanisms, measurement, and management, Mahler DA, O'Donnell DE (Eds), Marcel Dekker, New York 2005. p.115.
- Parshall MB, Schwartzstein RM, Adams L, et al. An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med 2012; 185:435.
- Scano G, Ambrosino N. Pathophysiology of dyspnea. Lung 2002; 180:131.
- Jensen D, Webb KA, Davies GA, O'Donnell DE. Mechanisms of activity-related breathlessness in healthy human pregnancy. Eur J Appl Physiol 2009; 106:253.
- Haugdahl HS, Storli SL, Meland B, et al. Underestimation of Patient Breathlessness by Nurses and Physicians during a Spontaneous Breathing Trial. Am J Respir Crit Care Med 2015; 192:1440.
- Banzett RB, Schwartzstein RM. Dyspnea: Don't Just Look, Ask! Am J Respir Crit Care Med 2015; 192:1404.
- Banzett RB, Pedersen SH, Schwartzstein RM, Lansing RW. The affective dimension of laboratory dyspnea: air hunger is more unpleasant than work/effort. Am J Respir Crit Care Med 2008; 177:1384.
- Banzett RB, Lansing RW, Reid MB, et al. 'Air hunger' arising from increased PCO2 in mechanically ventilated quadriplegics. Respir Physiol 1989; 76:53.
- Banzett RB, Lansing RW, Brown R, et al. 'Air hunger' from increased PCO2 persists after complete neuromuscular block in humans. Respir Physiol 1990; 81:1.
- Demediuk BH, Manning H, Lilly J, et al. Dissociation between dyspnea and respiratory effort. Am Rev Respir Dis 1992; 146:1222.
- Banzett RB, Lansing RW. Respiratory sensations arising from pulmonary and chemoreceptor afferents. In: Respiratory Sensation, Adams L, Guz A (Eds), Marcel Dekker Inc, New York 1996. p.155.
- Weese-Mayer DE, Berry-Kravis EM, Ceccherini I, et al. An official ATS clinical policy statement: Congenital central hypoventilation syndrome: genetic basis, diagnosis, and management. Am J Respir Crit Care Med 2010; 181:626.
- Chronos N, Adams L, Guz A. Effect of hyperoxia and hypoxia on exercise-induced breathlessness in normal subjects. Clin Sci (Lond) 1988; 74:531.
- Lane R, Cockcroft A, Adams L, Guz A. Arterial oxygen saturation and breathlessness in patients with chronic obstructive airways disease. Clin Sci (Lond) 1987; 72:693.
- Adams L, Lane R, Shea SA, et al. Breathlessness during different forms of ventilatory stimulation: a study of mechanisms in normal subjects and respiratory patients. Clin Sci (Lond) 1985; 69:663.
- Taguchi O, Kikuchi Y, Hida W, et al. Effects of bronchoconstriction and external resistive loading on the sensation of dyspnea. J Appl Physiol (1985) 1991; 71:2183.
- Moy ML, Woodrow Weiss J, Sparrow D, et al. Quality of dyspnea in bronchoconstriction differs from external resistive loads. Am J Respir Crit Care Med 2000; 162:451.
- McBride B, Whitelaw WA. A physiological stimulus to upper airway receptors in humans. J Appl Physiol Respir Environ Exerc Physiol 1981; 51:1189.
- Schwartzstein RM, Lahive K, Pope A, et al. Cold facial stimulation reduces breathlessness induced in normal subjects. Am Rev Respir Dis 1987; 136:58.
- Spence DP, Graham DR, Ahmed J, et al. Does cold air affect exercise capacity and dyspnea in stable chronic obstructive pulmonary disease? Chest 1993; 103:693.
- Simon PM, Basner RC, Weinberger SE, et al. Oral mucosal stimulation modulates intensity of breathlessness induced in normal subjects. Am Rev Respir Dis 1991; 144:419.
- FOWLER WS. Breaking point of breath-holding. J Appl Physiol 1954; 6:539.
- Chonan T, Mulholland MB, Cherniack NS, Altose MD. Effects of voluntary constraining of thoracic displacement during hypercapnia. J Appl Physiol (1985) 1987; 63:1822.
- Schwartzstein RM, Simon PM, Weiss JW, et al. Breathlessness induced by dissociation between ventilation and chemical drive. Am Rev Respir Dis 1989; 139:1231.
- O'Donnell DE, Bertley JC, Chau LK, Webb KA. Qualitative aspects of exertional breathlessness in chronic airflow limitation: pathophysiologic mechanisms. Am J Respir Crit Care Med 1997; 155:109.
- Nishino T, Ide T, Sudo T, Sato J. Inhaled furosemide greatly alleviates the sensation of experimentally induced dyspnea. Am J Respir Crit Care Med 2000; 161:1963.
- Moosavi SH, Binks AP, Lansing RW, et al. Effect of inhaled furosemide on air hunger induced in healthy humans. Respir Physiol Neurobiol 2007; 156:1.
- Jensen D, Amjadi K, Harris-McAllister V, et al. Mechanisms of dyspnoea relief and improved exercise endurance after furosemide inhalation in COPD. Thorax 2008; 63:606.
- Simon PM, Schwartzstein RM, Weiss JW, et al. Distinguishable sensations of breathlessness induced in normal volunteers. Am Rev Respir Dis 1989; 140:1021.
- Manning HL, Schwartzstein RM. Pathophysiology of dyspnea. N Engl J Med 1995; 333:1547.
- Manning HL, Basner R, Ringler J, et al. Effect of chest wall vibration on breathlessness in normal subjects. J Appl Physiol (1985) 1991; 71:175.
- Sibuya M, Yamada M, Kanamaru A, et al. Effect of chest wall vibration on dyspnea in patients with chronic respiratory disease. Am J Respir Crit Care Med 1994; 149:1235.
- Cristiano LM, Schwartzstein RM. Effect of chest wall vibration on dyspnea during hypercapnia and exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997; 155:1552.
- Homma I, Obata T, Sibuya M, Uchida M. Gate mechanism in breathlessness caused by chest wall vibration in humans. J Appl Physiol Respir Environ Exerc Physiol 1984; 56:8.
- Banzett RB, Lansing RW, Brown R. High-level quadriplegics perceive lung volume change. J Appl Physiol (1985) 1987; 62:567.
- Manning HL, Shea SA, Schwartzstein RM, et al. Reduced tidal volume increases 'air hunger' at fixed PCO2 in ventilated quadriplegics. Respir Physiol 1992; 90:19.
- McCloskey DI. Corollary discharges: Motor commands and perception. In: Handbook of Physiology, Section I, The Nervous System, Brookahrt JM, Mountcastle VB (Eds), American Physiological Society, Bethesda 1981. Vol II, p.1415.
- Killian KJ, Gandevia SC, Summers E, Campbell EJ. Effect of increased lung volume on perception of breathlessness, effort, and tension. J Appl Physiol Respir Environ Exerc Physiol 1984; 57:686.
- Schwartzstein RM, Manning HL, Weiss JW, Weinberger SE. Dyspnea: a sensory experience. Lung 1990; 168:185.
- O'Donnell DE, Webb KA. Exertional breathlessness in patients with chronic airflow limitation. The role of lung hyperinflation. Am Rev Respir Dis 1993; 148:1351.
- O'Donnell DE, Banzett RB, Carrieri-Kohlman V, et al. Pathophysiology of dyspnea in chronic obstructive pulmonary disease: a roundtable. Proc Am Thorac Soc 2007; 4:145.
- Lougheed MD, Fisher T, O'Donnell DE. Dynamic hyperinflation during bronchoconstriction in asthma: implications for symptom perception. Chest 2006; 130:1072.
- Manning HL, Molinary EJ, Leiter JC. Effect of inspiratory flow rate on respiratory sensation and pattern of breathing. Am J Respir Crit Care Med 1995; 151:751.
- Clark AL, Piepoli M, Coats AJ. Skeletal muscle and the control of ventilation on exercise: evidence for metabolic receptors. Eur J Clin Invest 1995; 25:299.
- Clark A, Volterrani M, Swan JW, et al. Leg blood flow, metabolism and exercise capacity in chronic stable heart failure. Int J Cardiol 1996; 55:127.
- Killian KJ, Leblanc P, Martin DH, et al. Exercise capacity and ventilatory, circulatory, and symptom limitation in patients with chronic airflow limitation. Am Rev Respir Dis 1992; 146:935.
- Corfield DR, Fink GR, Ramsay SC, et al. Evidence for limbic system activation during CO2-stimulated breathing in man. J Physiol 1995; 488 ( Pt 1):77.
- Banzett RB, Mulnier HE, Murphy K, et al. Breathlessness in humans activates insular cortex. Neuroreport 2000; 11:2117.
- Peiffer C, Poline JB, Thivard L, et al. Neural substrates for the perception of acutely induced dyspnea. Am J Respir Crit Care Med 2001; 163:951.
- von Leupoldt A, Sommer T, Kegat S, et al. Down-regulation of insular cortex responses to dyspnea and pain in asthma. Am J Respir Crit Care Med 2009; 180:232.
- Lansing RW, Gracely RH, Banzett RB. The multiple dimensions of dyspnea: review and hypotheses. Respir Physiol Neurobiol 2009; 167:53.
- Meek PM, Banzett R, Parshall MB, et al. Reliability and validity of the multidimensional dyspnea profile. Chest 2012; 141:1546.
- Janssens T, De Peuter S, Stans L, et al. Dyspnea perception in COPD: association between anxiety, dyspnea-related fear, and dyspnea in a pulmonary rehabilitation program. Chest 2011; 140:618.
- INCREASED OUTPUT FROM THE RESPIRATORY CENTERS
- Acute hypercapnia
- Acute hypoxemia
- STIMULATION OF MECHANORECEPTORS
- Upper airway receptors
- Pulmonary receptors
- Chest wall receptors
- MECHANICAL LOADING OF THE RESPIRATORY SYSTEM
- NEUROMECHANICAL DISSOCIATION
- IMPAIRED OXYGEN DELIVERY OR UTILIZATION
- NEURAL ACTIVATION ASSOCIATED WITH BREATHING DISCOMFORT
- The affective dimension of dyspnea